A vast number of biomolecules and biological entities (such as proteins and other complex molecules, and bacteria, fungal cells and other cell types) can be detected using immunologic techniques. Common among these tests, and well-known in the art, are ELISA (Enzyme-Linked ImmunoSorbent Assay) tests. Typically an ELISA test's target (the antigen) has molecular properties for which binding domains of antibodies have affinity. Antibodies are molecules that “fit” and bind to the antigen; the binding can be strong or weak. In order to identify those biomolecules and biological entities that are bound by specific antibodies, a tag (in this case, an enzyme) is typically attached to the antibodies. These tags react with additional chemical markers that, after enzymatic catalysis, fluoresce or cause the solution to change color. Other immunologic tests use radioactive tags (e.g., radio-immuno assay, or RIA, tests).
All of these immunologic tests require multiple steps. In an ELISA test, for example, a first step is to attach target entities to a test well. A second step is to introduce a fluid containing tagged antibodies into the well. The tagged antibodies then bind with considerable specificity to matching antigens (and less so, or not at all, to the other entities that may be present in the well). After fluid is removed, the test well is rinsed to remove unbound antibodies (if a detection step is prematurely implemented before rinsing, all antibodies, whether tightly bound to antigen or unbound, may potentially be detected). Finally, the well is refilled with a neutral fluid and marker chemicals are added. A detection step is then implemented, and the presence or amount of antigen is determined from a color change or florescence measurement. A reliable and efficient means of minimizing or eliminating steps in immunosorbent assays is needed.
Testing of a liquid sample often requires manually adding a liquid reagent to the liquid sample followed by manually mixing the liquid sample and the added liquid reagent. For example, in order to test a liquid sample, a researcher may add, through the use of a micropipette, a liquid reagent to an aliquot of the liquid sample in a microtube. The researcher may then need to mix the liquid sample with the added liquid reagent by further repetitively drawing up and expelling the mixture from the micropipette into the microtube. User variability (e.g., that may result from fatigue on the part of the researcher) or method variability introduced by relying on such micropipette-based mixing may adversely effect the reliability of subsequent measurements (e.g., colorimetric readings of chemical reactions in the liquid mixture).
The mixing of liquids is accomplished in some methods of high throughput screening (e.g., utilizing standard 96-well, 384-well, 1536-well or 3456-well plates) through automated additions of liquids across rows of wells within plates. These high throughput screening methods, however, generally require extensive electromechanical equipment and computer programming support for implementation. A generally simpler system for effecting the simultaneous mixing of a plurality of liquids is often needed.